Cartilage abnormalities associated with defects of chondrocytic primary cilia in Bardet-Biedl syndrome mutant mice.
Cartilage abnormalities associated with defects of chondrocytic primary cilia in Bardet-Biedl syndrome mutant mice.
复制标题
DOI：
10.1002/jor.20855
复制
发表时间：
2009-08
影响因子：
2.8
通讯作者：
Morcuende, Jose A.
中科院分区：
文献类型：
--
作者：
Kaushik, Anjan P.;Martin, James A.;Zhang, Qihong;Sheffield, Val C.;Morcuende, Jose A.
初级纤毛存在于几乎所有哺乳动物细胞上，包括骨细胞、成纤维细胞和软骨细胞。然而，初级纤毛在这些细胞中的功能还没有得到广泛的研究，特别是软骨细胞。有趣的是，初级纤毛的缺陷会导致骨骼缺陷，如Bardet-Biedl综合征(BBS)中的多指，这是一种纤毛疾病，也会导致肥胖、视网膜病变和认知障碍。研究了纤毛蛋白Bbs1、Bbs2和Bbs6的野生型小鼠和突变型小鼠关节软骨和剑突软骨细胞的组织学和生化差异。免疫荧光显微镜下可见承重关节和非承重剑突的软骨细胞纤毛。突变小鼠和野生型小鼠在纤毛形态上没有明显差异。然而，在细胞培养中扩增软骨细胞并将其植入固体琼脂糖凝胶基质中后，发现突变小鼠培养的纤毛细胞比例显著低于野生型培养(p<；0.05)。此外，在藏红花-O染色的整个关节切片中，BBS突变小鼠的关节厚度(p<；0.05)和蛋白多糖含量饱和度(p<；0.05)显著低于野生型小鼠。此外，Bbs突变小鼠和野生型小鼠关节软骨细胞分布差异有统计学意义(p<；0.05)，表明突变小鼠关节软骨的变化与骨关节炎的早期体征相一致。这些数据表明，BBS基因及其在软骨细胞初级纤毛中的功能对于正常的关节软骨维持是重要的。
Primary cilia are found on nearly every mammalian cell, including osteocytes, fibroblasts, and chondrocytes. However, the functions of primary cilia have not been extensively studied in these cells, particularly chondrocytes. Interestingly, defects in the primary cilium result in skeletal defects such as polydactyly in Bardet-Biedl Syndrome (BBS), a ciliary disorder that also results in obesity, retinopathy, and cognitive impairments. Wild-type mice and mutant mice of the ciliary proteins Bbs1, Bbs2, and Bbs6 were evaluated with respect to histological and biochemical differences in chondrocytes from articular cartilage and xiphoid processes. Using immunofluorescence microscopy, chondrocytic cilia were visualized from the load-bearing joints and non-load-bearing xiphoid processes. Significant differences in ciliary morphology were not identified between mutant and wild-type mice. However, after expanding chondrocytes in cell culture and implanting them in solid agarose matrix, it was seen that the fraction of ciliated cells in cultures from mutant mice was significantly lower than in the wild-type cultures (p<.05). In addition, in Safranin-O-stained whole joint sections, Bbs mutant mice had significantly lower articular joint thickness (p<.05) and lower proteoglycan content saturation (p<.05) than wild-type mice. Moreover, there were statistically significant differences of cell distribution between Bbs mutant and wild-type mice (p<.05), indicating that mutant articular cartilage had changes consistent with early signs of osteoarthritis. These data indicate that Bbs genes and their functions in the chondrocytic primary cilium are important for normal articular cartilage maintenance.
登录
查看更多内容
影响因子：
13.6
作者：
Mykytyn, K;Sheffield, VC
通讯作者：
Sheffield, VC
影响因子：
2.4
作者：
Poole, CA;Zhang, ZJ;Ross, JM
通讯作者：
Ross, JM
影响因子：
3.9
作者：
Poole, CA;Jensen, CG;Wheatley, DN
通讯作者：
Wheatley, DN
影响因子：
64.5
作者：
Nachury, Maxence V.;Loktev, Alexander V.;Jackson, Peter K.
通讯作者：
Jackson, Peter K.
影响因子：
7.8
作者：
Piperno, G;Siuda, E;Henderson, S;Segil, M;Vaananen, H;Sassaroli, M
通讯作者：
Sassaroli, M